Diabetes is categorized into two types: type 1 diabetes, which is caused by destruction of pancreatic β cells and develops at younger ages, and type 2, which is a lifestyle-related disease and is common in older ages. In either type, once diabetes develops, the patient must undergo continued lifelong symptomatic treatment including diet therapy, exercise therapy, hypoglycemic medication (oral agents or insulin injection). No radical therapy for diabetes is available and the target population is expected to increase steadily in the future.
Before the onset of diabetes, insufficiency of insulin secretion or decreased insulin function (insulin resistance) is often found. It is particularly important in suppressing the onset of diabetes to maintain adequate insulin producing ability at the pre-onset stage. The main purpose of diabetic pharmaceuticals is, however, to suppress hyperglycemia accompanying the onset of diabetes and to eliminate the factor for diabetic complications; no treatment method for eliminating the fundamental cause of diabetes has been established. Moreover, although a wide variety of health foods aiming at prevention and/or risk reduction of diabetes are available in the market, their effect is to suppress the postprandial hyperglycemia, which does not lead to elimination of the fundamental cause.
Although regeneration of insulin-producing β cells can potentially be a radical therapy and have a preventive effect, the current researches in this field which have yielded practical results as the method for regenerating β cells present the approaches taking advantage of organ or cell transplantation, or gene therapy. Such approaches should inevitably depend on organ transplantation surgery, injections of biological macromolecules (protein), etc., thereby imposing a great burden on patients and markedly deteriorating their quality of life (QOL). Thus, compositions capable of activating regeneration of an organ, especially pancreatic β cells, by oral administration, have been desired.
It is conventionally known that substances such as conophylline and conophyllidine (Anticancer Res. vol. 14: p. 413-2418, 1994; and J. Nat. Prod. vol. 56: p. 1865-1871, 1993) activate regeneration of pancreatic β cells (Biomed. Pharmacol. vol. 57: p. 341-350, 2003). Further, it is known that conophylline has a function of significantly suppressing increased blood glucose levels when intraperitoneally administered to model animals of neonatal diabetes (Diabetes vol. 53: p. 2596-2602, 2004).
Further, conophylline is considered to be useful in increasing insulin-producing ability and/or insulin-secreting ability of non-neoplastic cells derived from the pancreas, preventing and/or treating a disease associated with lack of insulin, reducing blood glucose levels, inducing differentiation of non-neoplastic cells derived from the pancreas into insulin-producing cells, and so forth (WO 04/099215). Moreover, since leaves of conophylline-producing plants or their dried product, their extracts, etc. induce AR42J cells to differentiate into insulin-producing cells and/or reduce blood glucose levels, they are considered to be useful as health foods for preventing or improving diabetes and/or reducing blood glucose levels (WO05/099485).
Because of their low water solubility, however, these substances are extracted with an organic solvent, making it difficult to prepare an aqueous solution of conophylline and/or conophyllidine suitable for oral administration.